Nicotine stimulates branching and expression of SP-A and SP-C mRNAs in embryonic mouse lung culture.
Although the effects of maternal smoking on fetal growth and viability are overwhelmingly negative, there is a paradoxical enhancement of lung maturation as evidenced, in part, by a lower incidence of respiratory distress syndrome in infants of smoking mothers. Other epidemiologic and experimental evidence further support the view that a tobacco smoke constituent, possibly nicotine, affects the development of the lung in utero. We are studying the direct effects of nicotine on murine lung development using a serumless organ culture system. We have found that embryonic lungs explanted at 11 days gestation showed a 32% increase in branching after 4 days in culture in the presence of 1 microM nicotine and 7- to 15-fold increases in mRNAs encoding surfactant proteins A and C after 11 days. The effect of nicotine exposure on surfactant gene expression is apparently mediated by nicotinic acetylcholine receptors because it was blocked by D-tubocurarine. The nicotine-induced stimulation of surfactant gene expression could, in part, account for the effect of maternal smoking on the incidence of respiratory distress syndrome.
Wuenschell
C W
CW
Center for Craniofacial Molecular Biology, School of Dentistry, University of Southern California, Los Angeles 90033.
Zhao
J
J
Tefft
J D
JD
Warburton
D
D
D000818:Animals; D004622:Embryo, Mammalian; D005314:Embryonic and Fetal Development; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005865:Gestational Age; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D008168:Lung / Q000187:drug effects / Q000196:embryology* / Q000502:physiology; D051379:Mice; D009024:Morphogenesis / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D009924:Organ Culture Techniques; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011510:Proteolipids / Q000096:biosynthesis*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D012127:Respiratory Distress Syndrome, Newborn / Q000453:epidemiology; D012907:Smoking / Q000009:adverse effects; D014158:Transcription, Genetic / Q000187:drug effects*
D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D009538:Nicotine